The Function Study Of MTORC2 Complex Protein Rictor In Mouse Spermatogenesis

Spermatogenesis takes place in the seminiferous tubule,where germ cells undergo three successive developmental phases,spermatogonial,meiotic and spermiogenic,to fulfill spermatogenesis.At the beginning,undifferentiated spermatogonia undergo continuous self-renewal or mitotic division.Then,primary spermatocytes proceed with meiotic divisions to produce haploid,round-shaped spermatids.Subsequently,round spermatids undergo spermiogenesis and release into the epididymides.The proceeding of these interlinked spermatogenetic phases is critically contingent on Sertoli cells,which are highly polarized cells that provide versatile supports to germ cells.Disregulation of germ-Sertoli cell adhesions results in structural defects of the seminiferous epithelium and male sterility.Germ cells migrating from basal stem cell niche upwards into the lumen of seminiferous tubules,needs the help from Sertoli cells.This germ cell migration is facilitated by the blood-testis barrier(BTB)restructuring at stages Ⅷ—Ⅸ of the epithelial cycle.BTB is featured by Sertoli cell-Sertoli cell junctions involving tight junction(TJ),gap junction(GJ)and ectoplasmic specialization(ES).Accompanied by BTB remodeling,preleptotene spermatocytes traverse the old BTB into the adluminal compartement to initiate meiotic phase.Maintenance of blood-tissue barrier or cell-cell communication is widely important during spermatogenesis.Recent studies have established a specific role of the mTOR complex 2(mTORC2)in Sertoli cells with regard to blood-testis barrier(BTB)dynamics in mammalian testis.However,it remains elusive whether mTORC2 executes a parallel germline-exclusive function and/or mechanism during testicular development.Here we report the essentiality of mTORC2 in the male germline by conditional inactivation of the core component Rictor of mTORC2 complex.Mice mutant exhibited increased apoptotic cell death,delayed meiotic entry as well as spermiogenic failure,resulting in oligospermia and male infertility,but unexpectedly,did not show a significant impairment of meiotic process.RNA-seq profiling revealed the inappropriate expression of adhesion and migration-linked genes in Rictor deficient testis,the cellular basis of which was observed to be defective integrity of intercellular cell adhesion including BTB,evidenced by abnormal distribution of a E-catenin and N-cadherin.Our work provides a previously unidentified involvement of the germline mTORC2/Rictor in regulation of BTB architecture of seminiferous epithelium,implicating its coordinative and non-redundant role in orchestrating the spermatogenic program that ensures the timely meiotic entry and normal post-meiotic differentiation.